Evaluation of Mast Cell Density in Mucoepidermoid Carcinoma and Pleomorphic Adenoma

Statement of the Problem: Mast cells are round to elliptical cells that originate from bone marrow stem cells and enter the peripheral blood. By releasing inflammatory mediators, these cells are involved in type I hypersensitivity, wound healing, defense against pathogens, increased blood vessel formation, and destruction of the extracellular matrix. There are contradictory results regarding the role of mast cells in tumor lesions. Purpose: Considering the contradictory results and few studies on the density of mast cells in salivary tumors, the present study investigated and compared the density of mast cells in two common salivary gland tumors. Materials and Method: In the cross-sectional study after reviewing the records of patients referred to the Pathology Department of the School of Dentistry and Shahid Sadoughi Hospital in Yazd, 15 blocks of each of the mucoepidermoid carcinoma and pleomorphic adenoma tumors were taken. After Giemsa staining of the samples, the average of stained cells in 10 random fields under 400× magnification was counted. The results were analyzed using statistical tests of t-test, ANOVA, Chi-square, and Mann-Whitney in SPSS ver. 22. Results: The average mast cell counts in pleomorphic adenoma (4.2) was higher than muco-epidermoid carcinoma (1.7) but there was no significant relationship (p= 0.305). In mucoepidermoid carcinoma, the numbers of mast cells increased with increasing tumor grade (low: 0/467 moderate: 1/567 high: 2/983) and there was a significant relationship (p= 0.009). Conclusion: According to the results of the present study, it seems that the mast cells accumulation may be secondarily associated with inflammatory responses due to cell accumulation and tissue destruction by tumor cells.


Introduction
Mast cells (MCs) are inflammatory cells originating in the bone marrow that are present in most human tissues [1]. Mastzella first discovered granule-containing cells in connective tissue in 1877 and named them Paul Ehrlich [2]. These cells are involved in inflammatory reactions and immune responses such as type 1 hypersensitivity, wound healing, and defense against pathogens [3]. Studies have shown that some mediators in MCs granules such as tryptase, kimase, vascular endothelial growth factor, fibroblast growth factor 2, and transforming growth factor β stimulate the proliferation of fibroblasts, fibrosis, and angiogenesis. Tryptase is an important growth factor for epithelial cells and can lead to the formation of new blood vessels in the tumor. Overall, large number of proteases can cause extracellular matrix degeneration and an increase in tumor size [1].
Salivary gland tumors are an important group of head and neck cancers [4] . In general, the tumor growth and metastasis is regulated when a balance is reached between protumorigenic and antitumorigenic factors.
Local inflammation at the tumor site leads to the infiltration of various inflammatory cells including MCs [5] .
A number of tyrosine kinase inhibitors, as anti-cancer drugs, suppress MCs by inhibiting C-Kit. Considering the possible effect of MCs on cancer cells and stroma, in recent years, the quantity of MCs in head and neck tumors such as squamous cell carcinoma and melanoma has been studied [1] . However, contradictory results have been obtained regarding the role of MCs in tumor progression [5]. Considering the contradictory results and few studies on counting and investigating the role of MCs in salivary gland tumors, the present study investigated the MCs density in two common salivary gland tumors, including mucoepidermoid carcinoma (MEC) and pleomorphic adenoma (PA).

Materials and Method
In the present cross-sectional and analytical study,

Results
The present study was performed on 15 PA and 15 MEC samples. The demographic information of the samples is given in Table 1. After Giemsa staining, round, oval, or spindle-shaped MCs with purple granules were counted ( Figure 1). The average MCC in PA (4.2) was higher than MEC (1.7) but no significant difference was observed between the two groups (p= 0.305) ( Figure 2). Statistical analysis did not show a significant relationship between the average MCC and the age variable ( Table 2). The average MCC in the major and minor salivary glands as well as in men and women is given in Table 3. Mann-Whitney test did not show a significant relationship between the average MCC and the sex variable. Although the average MCC was higher in the major glands, non-parametric analyzes showed that this di-
In a study of normal mucosa, mild to severe dysplasia, and squamous cell carcinoma, Gomes et al. [18] found that MCs density was higher in oral squamous cell carcinoma than in other groups. These researchers believed that the presence of MCs was important for tumor growth and invasion, but it is not related to grades of tumor differentiation [18].
Mohtasham et al. [19] concluded that the MCs density in high microscopic grades is more than low grades of oral squamous cell carcinoma and this cell can play a role in the formation and progression of tumors through angiogenesis [19].
Nike et al. [20] also reported an inverse relationship between MCs density and the malignancy grade of tumors, including squamous cell carcinoma of the cervix.
They suggested that these cells might be related to cell differentiation [20]. However, Sharma et al. [21] found a direct relation between MC density and microscopic grade of oral squamous cell carcinoma [21].
Regarding the role of MCs in the formation of malignant tumors, Ranieri et al. [11] and Coussens et al. and impairment in their diagnosis and counting [11][12].
MCs-secreted mediators such as vascular endothelial growth factor and interleukin 8 can play a role in the formation of blood vessels and suppression of the immune system and provide the conditions for tumor formation [12].  [26][27][28][29][30][31].

Conclusion
Considering to higher number of MCs in benign tumors than malignant ones and increase of cells with increasing degree of malignancy, it seems that the MCs accumulation is related to the inflammatory responses caused by cell accumulation and tissue destruction by tumor cells and it has slight relationship with tumor growth and development.

Conflict of Interest
Authors declare that there are no conflicts of interest in this study.